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Updated: Jun 30, 2025

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Evolution-inspired engineering of nonribosomal peptide synthetases
Kenan A J Bozhüyük1,2,3, Leonard Präve1,2, Carsten Kegler1,2
1Max Planck Institute for Terrestrial Microbiology, Department of Natural Products in Organismic Interactions, 35043 Marburg, Germany.
Abstract:
Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired "eXchange Unit between T domains" (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.
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